Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice

Int J Mol Med. 2017 Aug;40(2):454-464. doi: 10.3892/ijmm.2017.3028. Epub 2017 Jun 14.

Abstract

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects
  • Carbon Tetrachloride*
  • Cell Line
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / pathology*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytokines / analysis
  • Cytokines / immunology
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Liver / drug effects*
  • Liver / immunology
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protective Agents / therapeutic use*
  • Serum Amyloid P-Component / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Protective Agents
  • Serum Amyloid P-Component
  • Carbon Tetrachloride